VOCs and Sensory Irritation Symptoms

Sensory irritation symptoms involve irritation of the eyes, nose, and throat. Skin irritation is also sometimes included. While it is clear that numerous VOCs can cause sensory irritation symptoms when airborne concentrations are sufficiently high, at the concentrations typically found in normal buildings the contribution of most indoor VOCs and SVOCs to sensory irritation remains uncertain. Chamber studies with controlled exposures have documented increases in sensory irritation symptoms in people when VOCs are intentionally added to the chamber air, but these studies have used VOCs at airborne concentrations well above the concentrations found in most non-industrial indoor environments [1, 2]. Various estimates have been developed of the airborne concentrations of VOCs needed to provoke sensory irritation. If formaldehyde (discussed below) is excluded, the estimated VOC concentrations needed to provoke sensory irritation generally far exceed the normally observed indoor concentrations of these VOCs [3-6]. (This would also exclude intermittent exposures during cleaning using potentially irritant sprays.) In a review, Wolkoff et al. [6] concluded that currently known VOCs emitted directly to indoors from the aforementioned indoor sources (except from chemical reactions) are unlikely to be present in office buildings at concentrations sufficient to cause sensory irritation. They suggested that reporting of sensory irritation might in fact be a consequence of VOC-caused odors which are interpreted as sensory irritation, but that indoor air may also contain currently unrecognized VOCs with the potential to cause sensory irritation. Some of these unrecognized irritant VOCs may be the products of indoor chemical reactions between less irritating VOCs and ozone.

Although individual VOCs (except possibly the highly irritant chemicals formaldehyde and acrolein) are normally not present indoors at concentrations sufficient to cause sensory irritation symptoms, a mixture of many VOCs is normally present in indoor air. Researchers have hypothesized that simultaneous exposures to a large number of indoor VOCs might cause irritation. Consequently, the possible association of TVOC concentrations with increases in sensory irritation symptoms has been investigated in several multi-building surveys of indoor air quality in which occupants reported health symptoms via a questionnaire. A review [2] of the relevant literature published before 1996 found that the results of many studies were inconclusive due to methodological or reporting limitations. The review panel provided conclusions from ten cross-sectional studies without these limitations. In seven of these studies, there was no association of TVOC concentrations with symptom prevalence rates. One study found an association of higher TVOC with increased SBS symptoms, one study found a possible connection with asthma symptoms, and one study found the TVOC concentration associated with a perception of dry and dusty air. More recently, a cross sectional study in offices [7-9] found that higher TVOC levels (> 666 g/m³) were associated with 50% to 90% increases in symptom prevalence rates for eye, skin, nose, throat, and mouth irritation symptoms and the increases were statistically significant in many cases; however, higher TVOC levels were generally not associated with objective (measured as opposed to reported) signs of sensory irritation. Two studies of schools were identified [10, 11] that report statistically significant increases in SBS symptoms in teachers or staff associated with increases in TVOC concentrations in schools. However, it is not certain that either study controlled for possible confounding by key potential confounding factors thus, the higher TVOC levels in these studies could have served as proxies for some other exposures or factors causally related to increased symptoms.

In summary, the evidence for an association of higher TVOC concentrations with sensory irritations symptoms is equivocal, with most studies not finding an association. Today, some indoor air researchers believe that measurements of TVOC have minimal value because the composition of individual VOCs within the indoor TVOC mixture varies widely among buildings and because the odor thresholds and potencies of the individual VOCs to cause sensory irritation also vary a great deal [12, 13] .

Some of the reported multi-building surveys in office buildings measured airborne concentrations of a broad range of individual VOCs. At least two of these studies found that, while individual VOCs were not associated with increased symptoms, higher indoor concentrations of some groups of VOCs were associated with increases in sensory irritation symptoms. One of these studies found increased symptoms among occupants of buildings with higher concentrations of VOCs attributed to cleaning products and water-based paints [14] and the second study found increased symptoms among occupants of buildings with higher concentrations of VOCs attributed to photocopiers and paints [15].

A number of recent studies have investigated associations of VOCs in homes with what are called sick building syndrome (SBS) symptoms among occupants. SBS symptoms, referred to in this website and other studies, include a set of symptoms that don’t clearly indicate specific illnesses, often including various eye, nose, and throat symptoms; dry, itching, or irritated skin; cough; fatigue, headache; nausea or dizziness; and difficulty concentrating. The SBS definition in most studies also includes that the symptoms occur more when the person is located in the building being studied, compared to when the person is elsewhere. SBS symptoms in homes are referred to in some studies as sick house syndrome (SHS).

An earlier Finnish study by Kostiainen [16] found that in homes with reported sick house symptoms, concentrations of multiple specific chemicals or of total chemicals exceeded “normal” levels more often than in the houses without these symptoms. “Normal” levels were defined as the median levels in a set of homes without occupants reporting symptoms. The specific chemicals with unusually high levels included aromatic hydrocarbons, terpenes, some alkylcyclohexanes, 1,1,1-trichloroethane, and tetrachloroethene. A number of studies from Japan have reported associations between increased SBS symptoms among occupants in new homes and higher airborne concentrations of total VOCs or  specific VOCs including toluene, butyl acetate, ethylbenzene, alpha-pinene, p-dichlorobenzene, nonanal, and xylene [17];  formaldehyde and alpha-pinene [18]; and aldehydes and straight chain hydrocarbons [19, 20]. Takigawa et al. [19] also reported that SBS symptoms increased systematically as formaldehyde levels increased. Huang  et al. [21] found that formaldehyde and TVOCs were higher, but not statistically significantly so, in homes with SHS. Only one reported study focused on SVOCs and SHS [22]. This Japanese study, which measured eight plasticizers (materials used to soften plastics), 11 flame retardants, two alkyl phenol anti-oxidants, and one organochlorine synergist used in pesticides, found that higher levels of tributylphosphate, a plasticizer, and the organochlorine synergist were associated with increased mucosal symptoms in occupants, the plasticizer strongly so. Several chemicals (diethylphthalate and tris (2-butoxyethyl) phosphate) showed, unexpectedly, inverse associations with SHS symptoms, such that symptoms were reduced when the indoor concentration was higher.  These findings on VOCs and SVOCs, all from hypothesis-generating cross-sectional studies, are currently only suggestive.   

1.         Molhave, L., Chapter 25. Sensory irritation in humans caused by volatile organic compounds (VOCs) as indoor pollutants: a summary of 12 exposure experiments, in Indoor air quality handbook, J.D. Spengler, J.M. Samet, and J.F. McCarthy, Editors. 2000, McGraw Hill: New York. p. 25.1-25.28.

2.         Andersson, K., et al., TVOC and health in non-industrial indoor environments: report from a Nordic scientific consensus meeting at Langholmen in Stockholm, 1996. Indoor Air, 1997. 7(2): p. 78-91.

3.         Godish, T., Chapter 32. Aldehydes., in Indoor air quality handbook, J.D. Spengler, J.M. Samet, and J.F. McCarthy, Editors. 2000, McGraw Hill: New York. p. 32.1-32.22.

4.         Schaper, M., Development of a database for sensory irritants and its use in establishing occupational exposure limits. American Industrial Hygiene Association Journal, 1993. 54: p. 488-544.

5.         Wolkoff, P., et al., Formation of strong airway irritants in terpene/ozone mixtures. Indoor Air, 2000. 10(82-91).

6.         Wolkoff, P., et al., Organic compounds in office environments - sensory irritation, odor, measurements and the role of reactive chemistry. Indoor Air, 2006. 16(1): p. 7-19. https://dx.doi.org/10.1111/j.1600-0668.2005.00393.x.

7.         Brasche, S., et al., Factors determining different symptom patters of sick building syndrome syndrome - results from a multivariate analysis, in Indoor Air 1999. 1999, Construction Research Communications, Ltd., London: Edinburgh, Scotland. p. 402-407.

8.         Brasche, S., et al., Self-reported eye symptoms and related diagnostic findings--comparison of risk factor profiles. Indoor Air, 2005. 15 Suppl 10: p. 56-64. https://dx.doi.org/10.1111/j.1600-0668.2005.00358.x.

9.         Brasche, S., et al., Comparison of risk factor profiles concerning self-reported skin complaints and objectively determined skin symptoms in German office workers. Indoor Air, 2004. 14(2): p. 137-43. https://dx.doi.org/10.1046/j.1600-0668.2003.00222.x.

10.       Madureira, J., et al., Indoor air quality in schools and health symptoms among Portuguese teachers. Human and Ecological Risk Assessment, 2009. 15(1): p. 159-169. https://dx.doi.org/10.1080/10807030802615881.

11.       Norbäck, D., M. Torgen, and C. Edling, Volatile organic compounds, respirable dust, and personal factors related to prevalence and incidence of sick building syndrome in primary schools. Br J Ind Med, 1990. 47(11): p. 733-41. https://dx.doi.org/10.1136/oem.47.11.733.

12.       Cometto-Muniz, J.E., W.S. Cain, and M.H. Abraham, Detection of single and mixed VOCs by smell and by sensory irritation. Indoor Air, 2004. 14 Suppl 8: p. 108-17.

13.       Alarie, Y., G.D. Nielsen, and M.M. Schaper, Chapter 23. Animal bioassays for evaluation of indoor air quality, in Indoor Air Quality Handbook, J.D. Spengler, J.M. Samet, and J.F. McCarthy, Editors. 2000, McGraw Hill: New York. p. 23.1-23.49.

14.       Ten Brinke, J., et al., Development of new volatile organic compound (VOC) exposure metrics and their relationship to sick building syndrome symptoms. Indoor Air, 1998. 8: p. 140-152.

15.       Apte, M.G. and J.M. Daisey, VOCs and “sick building syndrome”: application of a new statistical approach for SBS research to U.S. EPA BASE Study data, in Indoor Air 99. 1999, Construction Research Communications, Ltd.: Edinburgh, Scotland. p. 117-122.

16.       Kostiainen, R., Volatile organic compounds in the indoor air of normal and sick houses. Atmospheric Environment, 1995. 29(6): p. 693-702. https://dx.doi.org/10.1016/1352-2310(94)00309-9.

17.       Saijo, Y., et al., Symptoms in relation to chemicals and dampness in newly built dwellings. International archives of occupational and environmental health, 2004. 77(7): p. 461-470. https://dx.doi.org/10.1007/s00420-004-0535-0.

18.       Takeda, M., et al., Relationship between sick building syndrome and indoor environmental factors in newly built Japanese dwellings. Int Arch Occup Environ Health, 2009. 82(5): p. 583-93.

19.       Takigawa, T., et al., Relationship between indoor chemical concentrations and subjective symptoms associated with sick building syndrome in newly built houses in Japan. International archives of occupational and environmental health, 2010. 83(2): p. 225-235. https://dx.doi.org/10.1007/s00420-009-0475-9.

20.       Takigawa, T., et al., A longitudinal study of aldehydes and volatile organic compounds associated with subjective symptoms related to sick building syndrome in new dwellings in Japan. Sci Total Environ, 2012. 417-418: p. 61-7. https://dx.doi.org/10.1016/j.scitotenv.2011.12.060.

21.       Huang, L.-l., et al., Field survey on the relation between IAQ and occupants' health in 40 houses in southern Taiwan. Journal of Asian Architecture and Building Engineering, 2011. 10(1): p. 249-256. https://dx.doi.org/10.3130/jaabe.10.249.

22.       Kanazawa, A., et al., Association between indoor exposure to semi-volatile organic compounds and building-related symptoms among the occupants of residential dwellings. Indoor Air, 2010. 20(1): p. 72-84. https://dx.doi.org/10.1111/j.1600-0668.2009.00629.x.

Formaldehyde and Sensory Irritation Symptoms

Numerous studies have investigated the potential of formaldehyde to cause irritation symptoms. Formaldehyde is present in outdoor air, but indoor concentrations are generally well above outdoor concentrations due to the presence of indoor sources including building materials, tobacco smoke, and chemical reactions involving ozone [1]. The studies of irritation from formaldehyde have included chamber studies with controlled short-term exposures to various formaldehyde concentrations; studies of health effects in workers exposed chronically to elevated formaldehyde levels at work; studies of occupants of mobile homes, which tended (at least in the past) to have moderately elevated formaldehyde concentrations relative to typical homes; and animal studies. Table 2 provides examples of guidelines based on sensory irritation effects.

Table 2. Examples of guidelines for formaldehyde, based on sensory irritation.

* REL developed using revised methodology [2].

** Associated health effect not unambiguously identified but likely to be irritation effect given the associated 15 minute exposure period

To place the formaldehyde guidelines based on sensory irritation in context, one must consider how they relate to indoor formaldehyde concentrations. From a review in 2003 of available data collected since 1990 [8] from convenience samples of U.S. homes (measurements collected in homes convenient to researchers without any assurance that the resulting sample of homes is representative of all U.S. homes), about half had a formaldehyde concentration above 17 ppb and 10% of homes had a concentration greater than 37 ppb. Because a small fraction of homes had much higher concentrations, the estimated overall average concentration in a U.S. home was 55 ppb. New homes tend to be more air tight and to have newer, stronger formaldehyde sources than older homes. In a survey of new homes in California, half of the houses had an indoor formaldehyde concentration greater than 29 ppb (36 µg/m³) and 25% had a concentration greater than 47 ppb (58 µg/m³) [9]. The outdoor concentrations of formaldehyde ranged from 0.16 to 6.5 ppb (0.2 to 8 µg/m³). From these data, it is clear that formaldehyde concentrations in most homes exceed the 8-hour and annual average guidelines of 7.2 ppb established by the California Environmental Protection Agency (EPA) to prevent respiratory effects, although fewer than 10% of houses exceed the 40 ppb 8-hour guideline from Health Canada for respiratory effects in children. Many homes, especially newer California homes, exceed the 1-hour guideline of 44 ppb from California EPA to protect from eye and airway irritation, but few homes are likely to have concentrations exceeding the higher guidelines established by other organizations to prevent sensory irritation.

With respect to the influence of formaldehyde in schools on sensory irritation symptoms, only one study was identified[10]. This study of 401 classrooms from 108 primary schools in France [10] reported a statistically significant increases in rhinoconjunctivitis (nasal congestion, runny nose, red or irritated eyes) with higher formaldehyde concentrations in classrooms. This study controlled for potential confounding by personal factors, but did not appear to control for concentrations of other indoor air pollutants. Therefore, the higher formaldehyde concentrations in this study might have served as a proxies for some other indoor pollutants causally related to increased symptoms.